Definition of two new epitopes on human immunodeficiency virus type 1 gag protein recognized by human CD8+ cytotoxic T lymphocyte clones.

We have established 3 CD8+ cytotoxic T lymphocyte (CTL) clones from the peripheral blood mononuclear cells of two HIV-1-seropositive asymptomatic donors. The epitopes recognized by these CTL clones were defined using synthetic peptides. The epitopes were located on HIV-1gag protein between amino acid (a.a.) 145 and 155 (QAISPRTLNAW), a.a.193 and 201 (GHQAAMQML), and a.a.260 and 267 (EIYKRWII), and were presented by HLA-A25, HLA-B38 and HLA-B8, respectively. The former 2 epitopes have not been previously defined.The HLA-A25-restricted epitope overlapped with HLA-B57-restricted and HLA-Cw3-restricted epitopes previously reported. In addition, this epitope overlapped with an HLA-DQ-restricted epitope recognized by CD4+ CTL. The HLA-B38-restricted epitope overlapped with HLA-A2-restricted and HLA-Bw52-restricted epitopes that were previously reported. The HLA-B38-restricted epitope between a.a.193 and 201 was highly conserved among HIV-1 strains. The results demonstrate that two new epitopes were defined in a region of gag protein that includes multiple epitopes presented by multiple HLA.     

A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group.

This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.     

Fatty acid profile of skeletal muscle phospholipid is altered in mdx mice and is predictive of disease markers

The mdx mouse is a model for Duchenne muscular dystrophy. The fatty acid (FA) composition in dystrophic muscle could potentially impact the disease severity. We tested FA profiles in skeletal muscle phospholipid (PL) and triglyceride in mdx and control (con) mice to assess associations with disease state as well as correlations with grip strength (which is lower in mdx) and serum creatine kinase (CK, which is elevated in mdx). Compared with con, mdx PL contained less docosahexaenoic acid (P < .001) and more linoleic acid (P = .001). Docosahexaenoic acid contents did not correlate with strength or serum CK. Linoleic acid content in PL was positively correlated with CK in mdx (P < .05) but not con. α-Linolenic acid content in PL was positively correlated with strength in mdx (P < .05) but not con. The FA profile in triglyceride showed less difference between groups and far less predictive ability for disease markers. We conclude that profiling the FA composition of tissue lipids (particularly PL) can be a useful strategy for generating novel biomarkers and potential therapeutic targets in muscle diseases and likely other pathological conditions as well. Specifically, the present results have indicated potential benefits of raising content of particular n-3 FAs (especially α-linolenic acid) and reducing content of particular n-6 FAs (linoleic acid) in PL of dystrophic muscle.